RESUMEN
Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy with classic adolescent onset of stimuli sensitive seizures. Patients typically deteriorate rapidly with dementia, ataxia, vegetative failure and death by 25 years of age. LD is caused by homozygous mutations in EPM2A or EPM2B genes. We found four novel mutations in EPM2A - three in exon 4 (Q247X, H265R G279C) and one in exon 1 (Y86D) - and a previously described mutation in exon 4 (R241X). These five EPM2A mutations were found in four index cases and affected relatives. Patient 1 with classic LD was doubly heterozygous for H265R and R241X in exon 4; while Patient 2, who also had classic LD, was homozygous for Q247X in exon 4. Patient 3 with classic LD was homozygous for Y86D in exon 1, but the same mutation in his affected brother manifested an atypical earlier childhood onset. For the first time, we describe a later onset and slower progression of EPM2A-deficient LD seen in Patient 4 and her three sisters who were doubly heterozygous for R241X and G279C in exon 4. In these sisters, seizures started later at 21 to 28 years of age and progressed slowly with patients living beyond 30 years of age. Our observations suggest that variations in phenotypes of EPM2A-deficient LD, like an earlier childhood or adolescent or later adult onset with a rapid or slower course, depend on a second modifying factor separate from pathogenicity or exon location of EPM2A mutations. A modifying gene amongst the patient's genetic background or environmental factors may condition age of onset and rapid or slow progression of LD.
Asunto(s)
Enfermedad de Lafora/genética , Mutación/genética , Proteínas Tirosina Fosfatasas no Receptoras/genética , Adulto , Análisis Mutacional de ADN , Electroencefalografía , Salud de la Familia , Femenino , Humanos , Enfermedad de Lafora/diagnóstico , MasculinoRESUMEN
UDP-glucuronosyltransferase 1A4 (UGT1A4) is a phase II drug-metabolizing enzyme that catalyzes the glucuronidation of many clinically-important drugs. Interethnic differences in the genetic polymorphism of UGT1A4 have been reported; however, there is no information in Mexican Mestizos (MMs) and Spaniards (SPs). Furthermore, MM is an admixed population with 26 % of Caucasian genes mainly from Spain. Therefore, this study aimed to investigate the potential differences between 318 SPs and 248 MMs healthy individuals regarding UGT1A4*1b, UGT1A4*2 and UGT1A4*3 alleles and to compare the observed frequencies with those previously reported in different populations. The allelic frequencies of the three UGT1A4 polymorphisms showed interethnic differences between MMs and SPs (p < 0.05). The analyzed SNPs variants in this genetic region were not in linkage disequilibrium (LD) for the MM population, suggesting that these mutations have arisen independently in the same genetic background. In contrast, UGT1A4*2 and UGT1A4*3 were in LD in the SP population. Comparison of present data with other in different ethnic groups revealed that the frequencies of UGT1A4*2 and UGT1A4*3 in SP were similar to other Caucasians and higher than in Asians, whereas in MMs were lower than in Caucasians and higher than in Asians only for UGT1A4*2. Present results could be helpful to improve the use of UGT1A4 drug substrates in order to adjust them to the ethnic background of a given population, specifically for Hispanics.
Asunto(s)
Estudios de Asociación Genética , Glucuronosiltransferasa/genética , Fase II de la Desintoxicación Metabólica/genética , Adulto , Anciano , Pueblo Asiatico , Femenino , Frecuencia de los Genes , Hispánicos o Latinos/genética , Humanos , Desequilibrio de Ligamiento , Masculino , Americanos Mexicanos/genética , México , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , España , Población Blanca/genéticaRESUMEN
PURPOSE: The purpose of this study was to identify the prevalence of mutations in the Myoclonin1/EFHC1 gene in Mexican patients with juvenile myoclonic epilepsy (JME). METHOD: We studied forty-one patients at the National Institute of Neurology and Neurosurgery in Mexico City and 100 healthy controls. DNA was extracted from the peripheral venous blood of all participants. The exons of EFHC1 were then amplified and sequenced. RESULTS: We found three new putative mutations, all of which were heterozygous missense mutations located in exon 3. The first identified mutation, 352C>T, produces a R118C change in the protein and cosegregated in the patient's affected father and brother. The second identified mutation, 544C>T, produces a R182L change in the protein and was found in the patient's asymptomatic father. The third identified mutation, 458>A, produces a R153Q change in the protein and was also found in the patient's father. These mutations were not found in controls. CONCLUSIONS: The frequency of Myoclonin1/EFHC1 mutations in our sample is 7.3%. Thus, we conclude that mutations in the Myoclonin1/EFHC1 gene are an important cause of JME in Mexican patients.
Asunto(s)
Proteínas de Unión al Calcio/genética , Epilepsia Mioclónica Juvenil/genética , Adolescente , Secuencia de Aminoácidos , Secuencia de Bases , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , México , Datos de Secuencia Molecular , Mutación Missense , Linaje , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Patients treated with antiepileptic drugs can exhibit large interindividual variability in clinical efficacy or adverse effects. This could be partially due to genetic variants in genes coding for proteins that function as drug metabolizing enzymes, drug transporters or drug targets. The purpose of this article is to provide an overview of the current knowledge on the pharmacogenetics of two commonly prescribed antiepileptic drugs with similar mechanisms of action; phenytoin (PHT) and lamotrigine (LTG). These two drugs have been selected in order to model the pharmacogenetics of Phase I and Phase II metabolism for PHT and LTG, respectively. In light of the present evidence, patients treated with PHT could benefit from CYP2C9 and CYP2C19 genotyping/phenotyping. For those under treatment with LTG, UGT1A4 and UGT2B7 genotyping might be of clinical use and could contribute to the interindividual variability in LTG concentration to dose ratio in epileptic patients.
Asunto(s)
Anticonvulsivantes/metabolismo , Fenitoína/metabolismo , Triazinas/metabolismo , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Hidrocarburo de Aril Hidroxilasas/genética , Hidrocarburo de Aril Hidroxilasas/metabolismo , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C9 , Epilepsia/tratamiento farmacológico , Genotipo , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Humanos , Lamotrigina , Farmacogenética , Fenitoína/efectos adversos , Fenitoína/uso terapéutico , Polimorfismo de Nucleótido Simple , Triazinas/efectos adversos , Triazinas/uso terapéuticoRESUMEN
Mutations in leucine-rich repeat kinase 2 gene (LRRK2) account for as much as 5-6% of familial Parkinson's disease (PD) and 1-2% of sporadic PD. These mutations represent the most frequent cause of autosomal dominant PD, particularly in certain ethnic groups. In this first report concerning LRRK2 mutations in Mexican-mestizos, we screened 319 consecutive PD patients (186 males; 133 females; mean age at onset: 52.4 years) for LRRK2 mutations in exons 31 and 41 and for the mutation in exon 35, which produces the Y1699C substitution. Three (0.94%) patients, two with sporadic PD and one with familial PD (disease mean age at onset, 53.3 years), were heterozygous for LRRK2 mutations. Of these three, two patients had one of two different mutations in exon 31 (R1441G and R1441H, respectively); the other patient carried the G2019S mutation in exon 41. The Y1699C mutation was absent from this PD sample. Four additional subjects, unaffected relatives of one PD patient with a mutation in LRRK2, were subsequently genetically tested. None of the three LRRK2 mutations identified was present in 200 neurologically healthy Mexican control individuals. These findings have important implications for molecular testing of LRRK2 mutations in Mexican PD patients.
Asunto(s)
Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Enfermedad de Parkinson/genética , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , México/epidemiología , Persona de Mediana Edad , Enfermedad de Parkinson/etnología , Enfermedad de Parkinson/metabolismo , Linaje , Adulto JovenRESUMEN
Huntington's disease (HD) is an autosomal dominant progressive, disabling neurodegenerative disorder, for which there is no effective treatment. Predictive testing (PT) for this illness began in 1986 and by 1993 it became more precise after cloning of the gene and the discovery of a CAG repeat expansion as the underlying cause. The objective of this paper is to illustrate the implementation and results of a PT program in a group of at-risk Mexican individuals with 12 years of follow-up. Our PT program conforms to the guidelines proposed by the International Huntington Association and the HD Working group of the World Federation of Neurology. Seventy-five individuals requested the testing, four of them did not fulfill the inclusion criteria, and five abandoned the program voluntarily before receiving the test results. Therefore, 66 results were delivered to 41 noncarriers and 25 mutation carriers. We did not have any catastrophic event, but 4 individuals with normal results and 11 mutation carriers were depressed. Even if this is a small sample, it is the first report of PT in a Latin-American population in which we have been faced with the same problems referred to in larger series.
Asunto(s)
Pruebas Genéticas , Enfermedad de Huntington/diagnóstico , Evaluación de Programas y Proyectos de Salud , Adulto , Análisis Mutacional de ADN , Femenino , Tamización de Portadores Genéticos , Heterocigoto , Humanos , Enfermedad de Huntington/genética , Masculino , México , MutaciónRESUMEN
We report the characteristics of 691 Mexican patients with Huntington's disease (HD). These patients, representing 401 families, constitute the largest series of Mexican HD cases as yet described in the literature. We found the clinical characteristics of these patients to be similar to those of other populations, but we observed a higher frequency of infantile cases, a shorter disease duration and a lower suicide rate. In 626 cases, for which molecular analyses were available, CAG-trinucleotide expansion size ranged from 37-106 repeats. The large number of CAG repeats (19.04 +/- 3.02) in normal alleles and the presence of new mutations suggest that the overall prevalence of HD in the Mexican population could be expected to be within range of, or higher than, that reported for Europeans.
Asunto(s)
Enfermedad de Huntington/genética , Enfermedad de Huntington/fisiopatología , Expansión de Repetición de Trinucleótido/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , Comparación Transcultural , Salud de la Familia , Femenino , Humanos , Masculino , México/epidemiología , México/etnología , Estudios Retrospectivos , Estadística como Asunto , Adulto JovenRESUMEN
Childhood absence epilepsy (CAE) accounts for 10% to 12% of epilepsy in children under 16 years of age. We screened for mutations in the GABA(A) receptor (GABAR) beta 3 subunit gene (GABRB3) in 48 probands and families with remitting CAE. We found that four out of 48 families (8%) had mutations in GABRB3. One heterozygous missense mutation (P11S) in exon 1a segregated with four CAE-affected persons in one multiplex, two-generation Mexican family. P11S was also found in a singleton from Mexico. Another heterozygous missense mutation (S15F) was present in a singleton from Honduras. An exon 2 heterozygous missense mutation (G32R) was present in two CAE-affected persons and two persons affected with EEG-recorded spike and/or sharp wave in a two-generation Honduran family. All mutations were absent in 630 controls. We studied functions and possible pathogenicity by expressing mutations in HeLa cells with the use of Western blots and an in vitro translation and translocation system. Expression levels did not differ from those of controls, but all mutations showed hyperglycosylation in the in vitro translation and translocation system with canine microsomes. Functional analysis of human GABA(A) receptors (alpha 1 beta 3-v2 gamma 2S, alpha 1 beta 3-v2[P11S]gamma 2S, alpha 1 beta 3-v2[S15F]gamma 2S, and alpha 1 beta 3-v2[G32R]gamma 2S) transiently expressed in HEK293T cells with the use of rapid agonist application showed that each amino acid transversion in the beta 3-v2 subunit (P11S, S15F, and G32R) reduced GABA-evoked current density from whole cells. Mutated beta 3 subunit protein could thus cause absence seizures through a gain in glycosylation of mutated exon 1a and exon 2, affecting maturation and trafficking of GABAR from endoplasmic reticulum to cell surface and resulting in reduced GABA-evoked currents.
Asunto(s)
Epilepsia Tipo Ausencia/genética , Epilepsia Tipo Ausencia/fisiopatología , Mutación Missense , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Secuencia de Aminoácidos , Línea Celular , Niño , Preescolar , Análisis Mutacional de ADN , ADN Complementario/genética , Electroencefalografía , Femenino , Ligamiento Genético , Genotipo , Glicosilación , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Fenotipo , Receptores de GABA-A/química , Homología de Secuencia de Aminoácido , TransfecciónRESUMEN
Spinocerebellar ataxia type 17 (SCA17) is caused by expansion of a CAG/CAA repeat in the TBP gene. Most pathogenic alleles are interrupted and are stably transmitted from parent to offspring without anticipation. We identified three SCA17 families with expansion of uninterrupted alleles, thus greatly increasing the number of known intergenerational transmissions of such alleles. We found that uninterrupted SCA17 alleles are unstable, associated with anticipation, and show a paternal expansion bias that increases with age. Even small increments in repeat length resulted in inordinate increases in anticipation. Anticipation was also associated with childhood presentation. Sequencing of all SCA17 alleles is required for effective genetic counseling.
Asunto(s)
Anticipación Genética , Ataxias Espinocerebelosas/genética , Proteína de Unión a TATA-Box/genética , Expansión de Repetición de Trinucleótido/genética , Adolescente , Adulto , Edad de Inicio , Alelos , Niño , Progresión de la Enfermedad , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Linaje , Distribución por Sexo , Ataxias Espinocerebelosas/diagnósticoRESUMEN
We investigated the association between apolipoprotein E (APOE) alleles and genotypes and Parkinson disease (PD) in 229 unrelated Mexican Mestizo PD patients and 229 controls. Results showed that both APOE-epsilon4 allele and APOE epsilon4/epsilon3 genotype are associated with PD (OR = 1.736, P = 0.011; OR = 1.688, P = 0.019, respectively). Mean age at onset of PD was not associated to any APOE allele or genotype, but was significantly earlier in familial PD when compared to sporadic cases (P = 0.025).
Asunto(s)
Apolipoproteína E4/genética , Predisposición Genética a la Enfermedad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Riesgo , Edad de Inicio , Anciano , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , México/epidemiología , Persona de Mediana EdadRESUMEN
La enfermedad de Huntington (EH) es un trastorno genético caracterizado por movimientos anormales, demencia y trastornos neuro-conductuales, con una herencia autosómica dominante. Su etiología es debida a una expansión de tripletes repetidos CAG en el gen HD localizado en el cromosoma 4p16.3, causando 36-121 repeticiones. Describimos a dos pacientes hondureños, miembros de una misma familia, con diagnóstico molecular de EH. El paciente índice se presentó con dificultad para de ambular, disartria, blefaroespasmo y movimientos involuntarios de manos, brazos y pies. Adicionalmente, pérdida de memoria,dificultad para la comprensión de tareas complejas, dificultad para realizar tareas de la vida diaria y pérdida de peso. Asimismo, se discuten las características neuropsiquiátricas de la enfermedad y asuntos éticos de importancia...
Asunto(s)
Persona de Mediana Edad , Corea , Demencia , Enfermedad de Huntington/diagnóstico , Trastornos Neurológicos de la MarchaRESUMEN
The etiology of Alzheimer's disease (AD) is complex. To date, molecular genetic studies in several families affected with AD have identified three genes associated with highly penetrant early-onset AD: Presenilin 1 (PSEN1), Presenilin 2 (PSEN2) and beta-amyloid precursor protein (APP); and one gene (apolipoprotein E) associated with late-onset AD. Molecular analysis of the PSEN1 gene was performed by direct sequencing of genomic DNA. The possible founder effect was investigated analyzing two highly polymorphic microsatellite markers flanking the PSEN1 gene. Twelve unrelated Mexican families with early-onset AD were analyzed. The Ala431Glu mutation in exon 12 of PSEN1 was found in nine (75%) of these families, which segregated showing autosomal dominant inheritance. Because all families bearing the mutation are from the State of Jalisco (located in Western Mexico), a founder effect was hypothesized. Microsatellite haplotype analysis suggested a common ancestor in these nine kindreds. In conclusion, the Ala431Glu mutation is a prevalent cause of early-onset familial Alzheimer's disease in families from the State of Jalisco, Mexico. Genetic evidence supports that it is a founder mutation descending from a single common ancestor. These findings have important implications for prompt diagnosis and genetic counseling for Mexican patients with familial AD from Jalisco.
Asunto(s)
Enfermedad de Alzheimer/genética , Efecto Fundador , Predisposición Genética a la Enfermedad , Mutación Missense , Presenilina-1/genética , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/etiología , Apolipoproteínas E/genética , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
The 2001 classification subcommittee of the International League Against Epilepsy (ILAE) proposed to 'group JME, juvenile absence epilepsy, and epilepsy with tonic clonic seizures only under the sole heading of idiopathic generalized epilepsies (IGE) with variable phenotype'. The implication is that juvenile myoclonic epilepsy (JME) does not exist as the sole phenotype of family members and that it should no longer be classified by itself or considered a distinct disease entity. Although recognized as a common form of epilepsy and presumed to be a lifelong trait, a long-term follow-up of JME has not been performed. To address these two issues, we studied 257 prospectively ascertained JME patients and encountered four groups: (i) classic JME (72%), (ii) CAE (childhood absence epilepsy) evolving to JME (18%), (iii) JME with adolescent absence (7%), and (iv) JME with astatic seizures (3%). We examined clinical and EEG phenotypes of family members and assessed clinical course over a mean of 11 +/- 6 years and as long as 52 years. Forty per cent of JME families had JME as their sole clinical phenotype. Amongst relatives of classic JME families, JME was most common (40%) followed by grand mal (GM) only (35%). In contrast, 66% of families with CAE evolving to JME expressed the various phenotypes of IGE in family members. Absence seizures were more common in family members of CAE evolving to JME than in those of classic JME families (P < 0.001). Female preponderance, maternal transmission and poor response to treatment further characterized CAE evolving to JME. Only 7% of those with CAE evolving to JME were seizure-free compared with 58% of those with classic JME (P < 0.001), 56% with JME plus adolescent pyknoleptic absence and 62% with JME plus astatic seizures. Long-term follow-up (1-40 years for classic JME; 5-52 years for CAE evolving to JME, 5-26 years for JME with adolescent absence and 3-18 years for JME with astatic seizures) indicates that all subsyndromes are chronic and perhaps lifelong. Seven chromosome loci, three epilepsy-causing mutations and two genes with single nucleotide polymorphisms (SNPs) associating with JME reported in literature provide further evidence for JME as a distinct group of diseases.
Asunto(s)
Epilepsia Mioclónica Juvenil/genética , Adolescente , Adulto , Edad de Inicio , Niño , Enfermedad Crónica , Progresión de la Enfermedad , Electroencefalografía , Familia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Epilepsia Mioclónica Juvenil/clasificación , Fenotipo , Polimorfismo de Nucleótido Simple , Pronóstico , Factores SexualesRESUMEN
Idiopathic generalized epilepsies (IGEs) comprise at least 40% of epilepsies in the United States, 20% in Mexico, and 8% in Central America. Here, we review seizure phenotypes across IGE syndromes, their response to treatment and advances in molecular genetics that influence nosology. Our review included the Medline database from 1945 to 2005 and our prospectively collected Genetic Epilepsy Studies (GENESS) Consortium database. Generalized seizures occur with different and similar semiologies, frequencies, and patterns, ages at onset, and outcomes in different IGEs, suggesting common neuroanatomical pathways for seizure phenotypes. However, the same seizure phenotypes respond differently to the same treatments in different IGEs, suggesting different molecular defects across syndromes. De novo mutations in SCN1A in sporadic Dravet syndrome and germline mutations in SCN1A, SCN1B, and SCN2A in generalized epilepsies with febrile seizures plus have unraveled the heterogenous myoclonic epilepsies of infancy and early childhood. Mutations in GABRA1, GABRG2, and GABRB3 are associated with absence seizures, while mutations in CLCN2 and myoclonin/EFHC1 substantiate juvenile myoclonic epilepsy as a clinical entity. Refined understanding of seizure phenotypes, their semiology, frequencies, and patterns together with the identification of molecular lesions in IGEs continue to accelerate the development of molecular epileptology.
Asunto(s)
Epilepsia Generalizada/clasificación , Epilepsia Generalizada/genética , Adolescente , Adulto , Distribución por Edad , Anticonvulsivantes/uso terapéutico , Niño , Preescolar , Epilepsia Generalizada/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Biología Molecular , Mutación/genética , Fenotipo , Pronóstico , SíndromeRESUMEN
OBJECTIVE: Although CYP2D6 genetic polymorphism plays an important role in interindividual and interethnic variability in drug response, very few pharmacogenetic data are available from Hispanic populations, including Mexicans. For this purpose, this study was undertaken to determine CYP2D6 genotype and phenotype in a healthy Mexican Mestizo population. METHODS: Genotyping of five CYP2D6 mutant alleles by PCR-RFLP, and CYP2D6*5 and duplicated CYP2D6 alleles by long-PCR was performed in two hundred and forty three Mexican Mestizos. Of these, one hundred subjects were also phenotyped using dextromethorphan as the probe drug. RESULTS: The frequency of CYP2D6*2, *3, *4, *5, *10, *17 was 19.34%, 1.44%, 11.21%, 2.67%, 12.45%, and 1.65%, respectively, while duplicated CYP2D6 alleles were found in 12.76% of the 243 genotyped subjects. Among the 100 phenotyped subjects, we identified ten (10%, 95% confidence interval of 4.12-15.9) individuals as poor metabolizers by using the published antimode for Caucasians. The mean log10 dextromethorphan/dextrorphan ratio of the total sample was -2.05. The mean (SD) of the log10 MR in the CYP2D6 subgroups was UM = -2.6 (0.86); EM = -2.09 (0.98); IM = -1.71 (1.06); and PM = 0.42 (0.625). These data show a trend toward a smaller mean log MR (higher enzyme activity) as the number of active alleles increases. CONCLUSIONS: The PM frequency of CYP2D6 in the population studied was 10%, which is very similar to Spanish Caucasians. The observed frequency of the CYP2D6 alleles tested was unique for the Mexican Mestizo sample analyzed, and in accordance to the Caucasian, Asian and African admixture in this population.
Asunto(s)
Citocromo P-450 CYP2D6/genética , Frecuencia de los Genes , Adulto , Alelos , Cromatografía Líquida de Alta Presión , ADN/genética , Dextrometorfano/farmacocinética , Dextrometorfano/orina , Femenino , Genética de Población , Genotipo , Humanos , Masculino , México/etnología , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de RestricciónAsunto(s)
Salud de la Familia , Epilepsia Mioclónica Juvenil/genética , Adolescente , Adulto , Edad de Inicio , Mapeo Cromosómico/métodos , Demografía , Electroencefalografía/métodos , Epilepsia/complicaciones , Epilepsia Tipo Ausencia/complicaciones , Epilepsia Tipo Ausencia/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Epilepsia Mioclónica Juvenil/clasificación , Epilepsia Mioclónica Juvenil/etiología , Fenotipo , Riesgo , Factores SexualesRESUMEN
Understanding the latest advances in the molecular genetics of the epilepsies is important, as it provides a basis for comprehending the new practice of epileptology. Epilepsies have traditionally been classified and subtyped on the basis of clinical and neurophysiologic concepts. However, the complexity and variability of phenotypes and overlapping clinical features limit the resolution of phenotype-based classification and confound epilepsy nosology. Identification of tightly linked epilepsy DNA markers and discovery of epilepsy-causing mutations provide a basis for refining the classification of epilepsies. Recent discoveries regarding the genetics surrounding certain epilepsy types (including Lafora's progressive myoclonic epilepsy, the severe myoclonic epilepsy of infancy of Dravet, and idiopathic generalized epilepsies) may be the beginning of a better understanding of how rare Mendelian epilepsy genes and their genetic architecture can explain some complexities of the common epilepsies.
Asunto(s)
Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/clasificación , HumanosRESUMEN
In the present study the olfactory system of hereditary ataxia patients was tested using the smell identification test. Two previous findings suggested a possible olfactory impairment in these patients. First, an olfactory dysfunction has been found in different neurodegenerative diseases, and second, human functional imaging has shown cerebellar activation during olfaction. As an initial approach to determine if cerebellar ataxia impairs the olfactory process, cerebellar ataxia patients, along with basal ganglia patients, were tested. The results show an olfactory deficit in both basal ganglia and hereditary ataxia patients. Further exploration of the olfactory capacities in hereditary ataxia is necessary to elucidate the specific nature of the deficits.
Asunto(s)
Enfermedades de los Ganglios Basales/complicaciones , Enfermedades de los Ganglios Basales/fisiopatología , Trastornos del Olfato/etiología , Degeneraciones Espinocerebelosas/complicaciones , Degeneraciones Espinocerebelosas/fisiopatología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Olfato/fisiologíaRESUMEN
O objetivo deste trabalho foi analisar a evolução do estado nutricional das crianças de uma vila popular da periferia de Porto Alegre, RS, durante sua participação no Programa do Leite, instituido pela Secretaria Municipal de Saúde e Serviço Social (SMSSS). O programa prevê o atendimento de crianças desnutridas, que receberão atendimento, orientação e suprimento alimentar na forma de leite em pó até serem consideradas em boas condições...